Natural history of adenomas by CT colonography Evelien Dekker Charlotte Tutein Nolthenius, Jaap Stoker

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1 Natural history of adenomas by CT colonography Charlotte Tutein Nolthenius, Jaap Stoker Academic Medical Center Amsterdam, the Netherlands

2 Possible conflicts of interest None

3 Colonoscopy.. plus polypectomy reduces CRC-mortality Zauber A. NEJM 2012

4 Introduction Colonoscopy: more and more adenomas & serrated lesions are detected and resected 90% of detected polyps measure 1-9mm Guidelines advise removal of all polyps + send for pathology

5 Introduction However, natural behaviour of polyps poorly studied - but seems slow mm polyps: 3-6.6% show advanced histology 2,3 % that becomes advanced?? Time-frame?? Result: removal of many polyps without clear clinical relevance & many surveillance colonoscopies.. 1. Muto T. Cancer 1975;36: Lieberman D, Gastroenterology 2008;135: Kim DH, American Journal Roentgenol 2007;188:940-4.

6 Introduction Study longitudinal growth of polyps: Endoscopy: polyps not to be removed.. CT colonography: small polyps are not removed

7 Introduction CT Colonography study Pickhardt et al: 306 small polyps, surveillance 2.3 yrs (1-7 yrs) 22% progressed 50% stable 28% regressed (10% disappeared) Histology 131 polyps: 91% of advanced adenomas had progressed vs 37% non-advanced 1 Pickhardt PJ, Lancet Oncol 2013;14:

8 Study Natural Course of Medium-sized Polyps during a 3-year Surveillance Interval: Linear and Volumetric Assessment with CT Colonography in Correlation with Histology Tutein Nolthenius CJ, Boellaard TNB, de Haan MC, Nio CYN, Thomeer MGJ, Bipat S, Montauban van Swijndregt AD, van de Vijver MJ, Biermann K, Kuipers EJ, Dekker E, Stoker J. Am J Gastro 2015;110:

9 Methods Patients Asymptomatic Participating in CRC screening trial 1 1 or 2 medium-sized polyps at initial CT colonography Procedure Surveillance CT colonography after 3 years Standard low-dose protocol (2 msv) 1. Stoop EM, Lancet Oncology 2012;13:55-64

10 Methods CT colonography analysis ViewForum, Philips Experienced observer Location, morphology and linear size + 2 observers polyp detection

11 Methods Volumetric measurements Retrospectively Different observer Vitrea, Toshiba Semi-automated

12 Methods Volumetric change over 3 year surveillance interval in % Progression ( 30% increase) Stable (<30% increase to <30% reduction) Regression ( 30% reduction)

13 Methods Colonoscopy 6 mm polyps Histopathology CRC Advanced adenoma Non-advanced adenoma Sessile serrated adenoma Hyperplastic polyp

14 Results 70 Patients underwent surveillance CTC 95 Polyps (6-9 mm) detected on index CTC 13 resolved 82 Polyps redetected on surveillance CTC

15 Results 95 polyps 35% Progression (33 polyps) 38% Stable (36 polyps) 27% Regression (26 polyps) Advanced adenomas: Advanced adenomas: 45% Advanced adenomas: 17% 0% Non-advanced adenomas: Non-advanced adenomas: 39% Non-advanced adenomas: 44% 23% Serrated adenomas: Serrated adenomas: 3% Serrated adenomas: 3% 0% Other: Other: 12% Other: 36% 77% 14% Resolution (13 polyps)

16 Characteristics of all 95 polyps according to the threshold of volumetric change (±30%) during the surveillance interval Progression (n=33) Stable (n=36) Regression a (n=26) All polyps (n=95) Location Proximal b 16 (48%) 15 (42%) 16 (62%) Rectosigmoid 17 (52%) 21 (58%) 10 (38%) Morphology Sessile 25 (76%) 31 (86%) 23 (88%) Pedunculated 5 (15%) 3 (8%) 1 (4%) Flat 3 (9%) 2 (6%) 2 (8%) Histology Advanced adenoma 15 (45%) 6 (17%) 0 Non-advanced adenoma 13 (39%) 16 (44%) 6 (23%) Serrated adenoma 1 (3%) 1 (3%) 0 Hyperplastic lesion 3 (9%) 6 (17%) 1 (4%) Unresected 1 (3%) 7 (19%) 19 (73%) Cancer Total /95 (22%) of 6-9mm polyps progressed to advanced adenoma

17 Results Surveillance CT colonography Stable (n=36) Progression (n=33) Regression (n=26) Advanced adenoma Size 10mm Tubulovillous Villous HGD 0 0 0

18 Conclusions 22% polyps 6-9 mm progressed to advanced neoplasia in 3 years, majority did not Most progressed just by size No cancers, no HGD developed

19 Conclusions Advanced adenomas at follow-up: Majority among growing polyps One-third of advanced adenomas remained stable None had regressed

20 Discussion Small study, but fixed follow-up at 3y Comparable results to Pickhardt-study 1 Accuracy CTC detection 6-9 mm polyps 100% Detection-rates of SSAs for CTC markedly lower than for colonoscopy 2 Per-polyp design, not same as per-patient as in setting of population screening 1. Pickhardt PJ, Lancet Oncol, 2013;14: IJspeert JEG. Am J Gastro 2016;111:

21 Implications Less aggressive approach for 6-9mm polyps? At CT colonography: surveillance Also for other colon-imaging modalities? For colonoscopy:??

22 Implications Need for better (bio-)markers for presence and prediction of advanced adenomas <-----> very early cancers Truly relevant lesions for the patient!!

23 Burden, risks, costs colonoscopy& polypectomy Cure & prevention CRC

24 Name of presenter

25 CT Colonography Measurement of polyps: Linear assessment Volumetric assessment Reliable 1 Predictor of polyps histology 2 Not routinely used 1. Pickhardt PJ, Am J Roentgenol 2006;186: Pickhardt PJ, Lancet Oncol, 2013;14:

26 Table Growth categories according to different volumetric thresholds Volumetric thresholds ±30% overall 45 mm 3 overall ±20% per year Progressing (n) Advanced adenomas 15 (45%) 12 (52%) 11 (46%) Non-advanced adenomas 13 (39%) 8 (35%) 10 (42%) Sessile serrated adenomas 1 (3%) 0 1 (4%) Hyperplastic lesions 3 (9%) 2 (9%) 2 (8%) Unresected polyps 1 (3%) 1 (4%) 0 Stable (n) Advanced adenomas 6 (17%) 8 (13%) 10 (18%) Non-advanced adenomas 16 (44%) 27 (44%) 25 (45%) Sessile serrated adenomas 1 (3%) 2 (3%) 1 (2%) Hyperplastic lesions 6 (17%) 7 (11%) 8 (15%) Unresected polyps 7 (19%) 18 (29%) 11 (20%) Regressing (n) Advanced adenomas 0 1 (10%) 0 Non-advanced adenomas 6 (23%) 0 0 Sessile serrated adenomas Hyperplastic lesions 1 (4%) 1 (10%) 0 Unresected polyps 19 (73%) 8 (80%) 16 (100%)

27 Table Change in polyp size according to different linear thresholds Linear thresholds ±21% overall a ±2.4 mm overall c ±1 mm per year b Progressing Advanced adenomas 13 (50%) 12 (75%) 10 (77%) Non-advanced adenomas 5 (19%) 2 (13%) 2 (15%) Serrated adenomas 1 (4%) 0 0 Hyperplastic lesions 4 (15%) 1 (6%) 0 Unresected polyps 3 (12%) 1 (6%) 1 (8%) Stable Advanced adenomas 8 (20%) 9 (15%) 11 (17%) Non-advanced adenomas 24 (59%) 31 (53%) 32 (49%) Serrated adenomas 1 (2%) 2 (3%) 2 (3%) Hyperplastic lesions 3 (7%) 6 (10%) 8 (12%) Unresected polyps 6 (15%) 11 (19%) 11 (17%) Regressing Advanced adenomas Non-advanced adenomas 6 (21%) 2 (10%) 1 (6%) Serrated adenomas Hyperplastic lesions 2 (7%) 2 (10%) 0 Unresected polyps 19 (71%) 16 (80%) 16 (94%) a According to Pickhardt et al, b according to/based on Pickhardt et al, c according to Bethea et al.

28 Results 101 patients with one or two 6-9 mm polyps 23 patients excluded a 78 patients underwent surveillance CTC 8 FP on index CT colonography 70 patients included in analyses 13 patients with only <6mm or no polyps 57 patients with 6mm polyps No follow-up Colonoscopy & polypectomy